Pan-American Collaborative Retina Study Group Research Articles

LESSONS LEARNED FROM PACORES IN PROLIFERATIVE DIABETIC RETINOPATHY MANAGEMENT, DATA FROM LATIN AMERICA AND SPAIN: The Asbury Lecture 2020.

To review the current literature on the management of proliferative diabetic retinopathy (PDR) and the challenges in the real-world setting. A review of the literature was performed on the therapeutic options for PDR, with a focus on the real-world data presented by the Pan-American Collaborative Retina Study Group. Data from clinical trials and previous literature have reported that intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is noninferior to the gold standard panretinal photocoagulation for treating PDR. However, PDR recurs rapidly after cessation of anti-VEGF therapy. This is especially important in the context of the diabetic population that is prone to loss to follow-up. In a real-world, prospective study, patients with prior panretinal photocoagulation followed by anti-VEGF therapy had higher rates of sustained PDR regression relative to anti-VEGF therapy alone. Owing to its transient therapeutic effect, anti-VEGF therapy in patients with diabetes can present a risk of recurrent retinal neovascularization and progression of PDR if follow-up cannot be guaranteed. A combined paradigm with less aggressive, immediate panretinal photocoagulation followed by anti-VEGF therapy should be considered in this population.

Journal Review

Journal Review

Intravitreal Bevacizumab in Diabetic Retinopathy. Recommendations from the Pan-American Collaborative Retina Study Group (PACORES): The 2016 Knobloch Lecture.

The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevacizumab as a preoperative, adjuvant therapy before vitrectomy for proliferative diabetic retinopathy.

Intravitreal bevacizumab monotherapy in myopic choroidal neovascularisation: 5-year outcomes for the PAN-American Collaborative Retina Study Group

PurposeTo report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia.MethodsRetrospective analysis of naive CNV secondary to myopia that underwent...

Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan-American Collaborative Retina Study group

Background/aimsTo report the long-term anatomical and functional outcomes of patients with centre-involved diabetic macular oedema (DME) treated with intravitreal bevacizumab (IVB).MethodsRetrospective case series. Patients diagnosed with centre-involved DME that were...

Small-Gauge Pars Plana Vitrectomy for the Management of Symptomatic Posterior Vitreous Detachment after Phacoemulsification and Multifocal Intraocular Lens Implantation: A Pilot Study from the Pan-American Collaborative Retina Study Group.

Purpose. To determine the efficacy of 23-gauge pars plana vitrectomy (PPV) for symptomatic posterior vitreous detachment (PVD) on visual acuity (VA) and quality after multifocal intraocular lenses (IOLs). Methods. In this prospective case series, patients who developed symptomatic PVD and were not satisfied with visual quality due to floaters and halos after multifocal IOL implantation underwent PPV. Examinations included LogMAR uncorrected visual acuity (UCVA), intraocular pressure, biomicroscopy, and indirect ophthalmoscopy at baseline and 1, 7, 30, and 180 days postoperatively. Ultrasonography and aberrometry were performed. The Visual Functioning Questionnaire 25 (VFQ-25) was administered preoperatively and at 30 days postoperatively. Both the postoperative UCVA and questionnaire results were compared to preoperative findings using the Wilcoxon test. Results. Sixteen eyes of 8 patients were included. VA significantly improved from 0.17 to 0.09 postoperatively (P = 0.017). All patients reported improvement of halos, glare, and floaters. VFQ-25 scores significantly improved in general vision (P = 0.023), near activities (P = 0.043), distance activities (P = 0.041), mental health (P = 0.011), role difficulties (P = 0.042), and driving (P = 0.016). Conclusion. PPV may increase UCVA and quality of vision in patients with bilateral multifocal IOLs and symptomatic PVD. Larger studies are advised.

Intravitreal infliximab for refractory pseudophakic cystoid macular edema: results of the Pan-American Collaborative Retina Study Group

Inflammation is the major etiologic factor in the development of pseudophakic cystoid macular edema (CME). Several soluble mediators of inflammation such as tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of ocular inflammation. The purpose of this study is to report the short-term visual and anatomic outcomes following intravitreal injections of infliximab in eyes with refractory CME secondary to cataract surgery. An interventional, retrospective study of 7 eyes with refractory CME that were injected with 1 mg of infliximab. The main outcome measures were best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 6-month follow-up. At the 6 month follow-up, BCVA improved from 1.14 ± 0.59 logMAR at baseline to 0.51 ± 0.35 logMAR (p = 0.0156). CMT also improved from 584 ± 159 μm at baseline to 327 ± 127 μm at 6 months (p = 0.0111). No systemic adverse events were reported in these patients. There was a single episode of uveitis that responded to topical steroids. Inhibition of TNF-α may be beneficial in the treatment of refractory pseudophakic CME.

Intravitreal Bevacizumab for Refractory Pseudophakic Cystoid Macular Edema: The Pan-American Collaborative Retina Study Group Results

Intravitreal Bevacizumab for Refractory Pseudophakic Cystoid Macular Edema: The Pan-American Collaborative Retina Study Group Results

Primary Intravitreal Bevacizumab for Diffuse Diabetic Macular Edema: The Pan-American Collaborative Retina Study Group at 24 Months

To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin; Genentech, Inc., San Francisco, CA; 1.25 or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the 2 different doses of intravitreal bevacizumab (IVB) used is presented. Retrospective, multicenter, interventional, comparative case series. The clinical records of 115 consecutive patients (139 eyes) with DDME at 11 centers from 8 countries were reviewed. Patients were treated with at least 1 intravitreal injection of 1.25 or 2.5 mg of bevacizumab. All patients were followed up for 24 months. Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at the baseline, 1-, 3-, 6-, 12-, and 24-month visits. Changes in BCVA and OCT results. The mean age of the patients was 59.4+/-11.1 years. The mean number of IVB injections per eye was 5.8 (range, 1-15 injections). In the 1.25-mg group at 1 month, BCVA improved from 20/150 (0.88 logarithm of the minimum angle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P<0.0001). The mean BCVA at 24 months was 20/75 (0.57 logMAR units; P<0.0001). Similar BCVA changes were observed in the 2.5-mg group: at 1 month, BCVA improved from 20/168 (0.92 logMAR units) to 20/118 (0.78 logMAR units; P = 0.02). The mean BCVA at 24 months was 20/114 (0.76 logMAR units; P<0.0001). In the 1.25-mg group, the mean central macular thickness (CMT) decreased from 466.5+/-145.2 microm at baseline to 332.2+/-129.6 microm at 1 month and 286.6+/-81.5 microm at 24 months (P<0.0001). Similar results were obtained in the 2.5-mg group. Primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 24 months. The results show no evident difference between IVB at doses of 1.25 or 2.5 mg.

Intravitreal Bevacizumab for Refractory Pseudophakic Cystoid Macular Edema: The Pan-American Collaborative Retina Study Group Results

To determine the feasibility, safety, and clinical effect of intravitreal (IVT) bevacizumab (Avastin; Genentech, Inc., San Francisco, CA) in patients with refractory cystoid macular edema (CME) after cataract surgery. Interventional, retrospective, multicenter study. Thirty-six eyes of 31 patients with refractory CME after cataract surgery and with a mean age of 68.2 years (range, 67-87 years). Patients were treated with at least 1 IVT injection of 1.25 or 2.5 mg bevacizumab. Patients were followed up for 12 months. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) by optical coherence tomography (OCT). Twenty-six eyes (72.2%) demonstrated improvement of BCVA (> or =2 Early Treatment Diabetic Retinopathy Study [ETDRS] lines), and no eye experienced worsening of visual acuity (> or =2 ETDRS lines). Mean baseline BCVA was 20/200 (0.96 logarithm of the minimum angle of resolution [logMAR] units), and the mean 12-month BCVA was 20/80 (0.62 logMAR units; P<0.0001). Optical coherence tomography demonstrated that mean CMT at baseline was 499.9 microm (range, 298-784 microm) and decreased to a mean of 286.1 microm (range, 168-499 microm) at 12 months (P<0.0001). Four (11%) eyes received 2 injections, 10 (27.8%) eyes received 3 injections, 10 (27.8%) eyes received 4 injections, 1 (2.8%) eye received 5 injections, and 1 (2.8%) eye received 6 injections. The mean number of injections was 2.7 (range, 1-6), and the mean interval between injections was 15.1 weeks (range, 4-45 weeks). No ocular or systemic adverse events were observed. Short-term results suggest that IVT bevacizumab is well tolerated in patients with refractory pseudophakic CME. Treated eyes had a significant improvement in BCVA and decrease in macular thickness by OCT at 12 months.

Comparing outcomes in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration treated with two different doses of primary intravitreal bevacizumab: results of the pan-american collaborative retina study group (PACORES) at the 12-month follow-up

To compare the total number of injections and the anatomic and best-corrected visual acuity (VA) response after injecting 1.25 or 2.5 mg of bevacizumab as needed in patients with primary choroidal neovascularization secondary to age-related macular degeneration (AMD) at 12 months. This was a retrospective, interventional, comparative multicenter study of 60 eyes treated with intravitreal bevacizumab (35 eyes, 1.25 mg; 25 eyes, 2.5 mg). The mean number of injections per eye was 3.8 in the 1.25-mg group and 3.2 in the 2.5-mg group (P = 0.2752). At 12 months, in the 1.25-mg group, 16 (46%) eyes gained > or =3 lines of Early Treatment Diabetic Retinopathy Study (ETDRS) VA and seven (20%) lost > or =3 lines of ETDRS VA. In the 2.5-mg group, 11 (44%) eyes improved by > or =3 lines, and four (16%) lost > or =3 lines (P = 1.000). At 12 months, in the 1.25-mg group, the mean central macular thickness decreased from 419 +/- 201 microm at baseline to 268 +/- 96 microm, compared with a decrease from 388 +/- 162 to 296 +/- 114 microm in the 2.5-mg group (P = 0.7896). There were no statistically significant differences between the two dose groups with regard to the number of injections, anatomic and VA outcomes.

Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up

To report the 12-month anatomic and ETDRS best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin) (1.25 mg or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the two different doses of intravitreal bevacizumab (IVB) utilized was made. We reviewed the clinical records of 82 consecutive patients (101 eyes) with DDME in this interventional retrospective multicenter study. All patients with a minimum follow-up of 12 months (mean 57.6 +/- 8.4 weeks) were included in this analysis. Patients underwent ETDRS best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and follow-up visits. The mean age of our patients was 59.7 +/- 9.3 years. The mean number of IVB injections per eye was three (range: one to six injections) at a mean interval of 14.1 +/- 10.5 weeks. In the 1.25 mg group at 1 month BCVA improved from 20/190, logMAR = 0.97 to 20/85, logMAR 0.62, a difference that was statistically significant (p = 0.0001). This improvement was maintained throughout the 3-, 6-, and 12-month follow-up. The mean final BCVA at 12 months was 20/76, logMAR = 0.58 (p < 0.001), a statistically significant difference from baseline BCVA. Similar BCVA changes were observed in the 2.5 mg group. In the 1.25 mg group, the mean central macular thickness (CMT) decreased from 419.1 +/- 201.1 microm at baseline to 295.11 +/- 91.5 microm at 1 month, 302.1 +/- 124.2 microm at 3 months, 313.4.1 +/- 96.3 microm at 6 months, and 268.2 +/- 95.5 microm at 12 months (p < 0.0001). Similar CMT changes were observed in the 2.5 mg group. Adverse events included transient high blood pressure in one patient (1.2%), transient increased intraocular pressure in one eye (1%), and tractional retinal detachment in one eye (1%). Primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 12 months. There seems to be no difference in our results between intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg. In addition, our results suggest the need for at least three injections a year to maintain the BCVA results.

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema

To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Primary Intravitreal Bevacizumab (Avastin) for Diabetic Macular Edema: Results from the Pan-American Collaborative Retina Study Group at 6-Month Follow-up

Primary Intravitreal Bevacizumab (Avastin) for Diabetic Macular Edema: Results from the Pan-American Collaborative Retina Study Group at 6-Month Follow-up

Primary intravitreal bevacizumab for the management of pseudophakic cystoid macular edema: Pilot study of the Pan-American Collaborative Retina Study Group

To determine the feasibility, safety, and clinical effect of primary intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME) after cataract surgery. Five institutions in Venezuela, Costa Rica, Puerto Rico, Peru, and Brazil. Twenty-eight eyes of 25 patients treated with at least 1 intravitreal injection of 1.25 mg or 2.50 mg of Avastin participated in this interventional retrospective multicenter study at 5 institutions from 5 countries. Baseline and follow-up visits included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination. The mean follow-up was 32 weeks (range 24 to 52 weeks). Twenty eyes (71.4%) had improved best corrected visual acuity (BCVA) (> or =2 ETDRS lines), and no eye had worse visual acuity (> or =2 ETDRS lines). The BCVA remained stable in 8 eyes (28.6%). The mean baseline BCVA was 20/160 (logMAR = 0.92) and the mean final BCVA, 20/63 (logMAR = 0.50); the difference was statistically significant (P<.0001). The mean central macular thickness at baseline (466.3 microm; range 208 to 784 microm) decreased significantly (264.5 microm; range 176 to 513 microm) by the end of follow-up (P<.0001). Eight eyes (28.6%) required a second injection and 4 (14.3%), a third injection. The mean interval between injections was 13 weeks (range 5 to 26 weeks). No ocular or systemic adverse events were observed. Short-term results suggest that primary intravitreal Avastin is well tolerated in patients with pseudophakic CME. Treated eyes had a significant improvement in BCVA and decrease in macular thickness by OCT.

Twelve-month safety of intravitreal injections of bevacizumab (Avastin®): results of the Pan-American Collaborative Retina Study Group (PACORES)

Vascular endothelial growth factor (VEGF) plays an important role in many diseases of the posterior pole that are characterized by macular edema and/or intraocular neovascularization. Recently anti-VEGF agents such as ranibizumab and pegaptanib sodium have been shown to be beneficial in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). However in most parts of the world, both pegaptanib sodium and ranibizumab are not readily available. Bevacizumab, a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been proposed as an alternative treatment option. A total of 1,265 consecutive patients were injected with bevacizumab for diseases such as proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusions, and CNV of several etiologies including ARMD at eight Latin American institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were excluded because they were injected once and lost to follow-up. The remaining 1,173 patients constitute the subjects of this retrospective, multicenter, open label, uncontrolled interventional case series that reports the cumulative systemic and ocular adverse events following intravitreal bevacizumab during 12 months of follow-up. Patients were examined at baseline and then monthly. If the patients were unable to attend the 12-month visit, a telephone interview was conducted to assess for possible systemic complications. A total of 4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All 1,173 patients were accounted for at the 12-month visit. Systemic adverse events were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents, five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two (0.17%) toe amputations and five (0.4%) deaths. Ocular complications included seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous retinal detachment and vitreous hemorrhage. Despite the limited follow-up, repeated intravitreal injections of either 1.25 mg or 2.5 mg of bevacizumab appears to be safe and well tolerated during the 1st year.

Primary Intravitreal Bevacizumab (Avastin) for Diabetic Macular Edema: Results from the Pan-American Collaborative Retina Study Group at 6-Month Follow-up

To report the 6-month anatomic and best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin) in patients with diabetic macular edema (DME). Interventional retrospective multicenter study at 6 centers from 6 countries of patients with DME. We reviewed the clinical records of 88 consecutive patients (110 eyes) with DME. Seventy-eight eyes of 64 consecutive patients with a minimum follow-up of 6 months and mean age of 59.7+/-9.3 years were included in this analysis. Patients were treated with at least one intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab and underwent Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and follow-up visits. Repeated-measures analysis of variance was used to compare mean values. Changes in BCVA, OCT, and FA. Mean follow-up was 6.31+/-0.81 months (range, 6-9). Sixteen (20.5%) eyes needed a second injection at a mean of 13.8 weeks (range, 4-28), and 6 eyes needed a third injection (7.7%) at a mean of 11.5 weeks (range, 5-20). The mean baseline BCVA was 0.87 (logarithm of the minimum angle of resolution), and the final mean BCVA was 0.6, a difference that was statistically significant (P<0.0001). Final BCVA analysis by subgroups demonstrated that 32 (41.1%) eyes remained stable, 43 (55.1%) improved > or =2 ETDRS lines of BCVA, and 3 (3.8%) decreased > or =2 ETDRS lines of BCVA. Mean central macular thickness at baseline by OCT was 387.0+/-182.8 mum and decreased to a mean of 275.7+/-108.3 at end of follow-up (P<0.0001). No ocular or systemic adverse events were observed. Primary intravitreal bevacizumab at doses of 1.25 to 2.5 mg seem to provide stability or improvement in VA, OCT, and FA in DME at 6 months. Follow-up is still short to make any specific treatment recommendations; however, the results appear promising. Evaluation in a multicenter randomized controlled clinical trial with longer follow-up is needed.